Single-cell immune profiling to distinguish responders and non-responders to immunotherapy in advanced liver cancer

Identification of an Immune Single Cell Transcriptomic Profile of Responder and Non-responder Hepatocellular Carcinoma Patients Treated With Immune-checkpoint Inhibitors

This research will see if single-cell RNA patterns in blood immune cells can predict which patients with advanced liver cancer respond to immunotherapy.

Quick facts

• Study type: Observational
• Enrollment: 20 (estimated)
• Ages: 18 Years to 90 Years
• Sex: All
• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia (Academic / other)
• Drugs / interventions: atezolizumab, bevacizumab, tremelimumab, durvalumab, immunotherapy
• Locations: 1 site (Pavia, Lombardy)
• Trial ID: NCT07273708 on ClinicalTrials.gov

What this trial studies

This observational study collects peripheral blood mononuclear cells (PBMCs) from adults with advanced hepatocellular carcinoma receiving first-line immune checkpoint regimens (atezolizumab plus bevacizumab or tremelimumab plus durvalumab). Investigators will perform single-cell transcriptomics on PBMCs before and after treatment to identify changes linked to clinical response. They will also test whether pre-treatment PBMC signatures predict which patients have durable responses. As an exploratory step, patient PBMCs previously exposed to checkpoint inhibitors will be co-cultured with matched tumor organoids to see if those laboratory models reflect actual clinical outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced hepatocellular carcinoma starting first-line immunotherapy (atezolizumab plus bevacizumab or tremelimumab plus durvalumab) who can give informed consent.

Not a fit: Patients with life expectancy under 12 months due to other diseases, active autoimmune or immune deficiency conditions, ongoing drug abuse, or recent other malignancies meeting exclusion criteria are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the study could help doctors predict who will benefit from immunotherapy and guide more personalized treatment decisions.

How similar studies have performed: Similar single-cell immune profiling approaches in other cancers have shown promising predictive signals, but prospectively validated blood-based signatures for HCC are still limited.

Eligibility criteria

Inclusion Criteria:

1. diagnosis of advanced HCC treated with atezolizumab plus bevacizumab or tremelimumab single dose plus durvalumab (STRIDE regimen) as first-line treament
2. age ≥18 and \<90 years at time of signing informed consent
3. Signed Informed Consent Form

Exclusion Criteria:

1. Life expectancy of \<12 months due to concomitant diseases
2. Active or history of autoimmune disease or immune deficiency on inflammatory chronic diseases
3. Ongoing drug abuse
4. History of malignancy other than HCC within 3 years prior to study entry with the following exception:

   1. Completely resected malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate 90%) and without evidence of recurrence for \> 3 years prior to study entry
   2. adequately treated non-melanoma skin carcinoma or lentigo maligna without evidence of metastases.
   3. adequately treated carcinoma in situ of the cervix without evidence of recurrence
   4. localised prostate cancer
   5. adequately treated non invasive or in situ urothelial cancers
5. evidence or history of positive HIV test
6. inability to comply with the study protocol, in the investigator's judgment

Where this trial is running

Pavia, Lombardy

• Fondazione IRCCS Policlinico San Matteo — Pavia, Lombardy, Italy (Recruiting)

Study contacts

• Study coordinator: Salvatore Corallo

Conditions Advanced HCC Treated by Systemic Immunotherapy; HCC Organoids; HCC PBMCs